Pharmacokinetic study of metformin intolerance

This pharmacokinetic study recruited white European individuals with type 2 diabetes, who had previously been exposed to metformin and met the criteria for tolerance or intolerance. Intolerance was defined as previous exposure to metformin (maximum of 1000mg once daily for up to 8 weeks) but discontinued treatment with patient reported or documentation of gastrointestinal upset, leading to discontinuation (Criterion 1). Alternatively, intolerance was defined as inability to increase metformin dose above 500mg without experiencing gastrointestinal side-effects, despite having an HbA1c >53mmol/mol (Criterion 2). Tolerant individuals were defined as those taking 2000mg metformin daily in divided doses, with no side effects. Ten tolerant and ten intolerant individuals were recruited.

Participants gave written consent. They attended the research centre fasted from midnight. A baseline blood test was taken before a single dose of oral metformin was administered at 0900, with further bloods taken at 11 time points over the following 24 hours. A 24 hour urine collection was completed.

Blood samples were analysed for plasma metformin, and serum lactate concentrations.

Inclusion Criteria:

• White European
• Type 2 diabetes
• Meet criteria for tolerance or intolerance as described

Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) <60
• Cognitive impairment
• Pregnancy
• Concurrent treatment with: acarbose, cephalexin, cimetidine, pyrimethamine, or tyrosine kinase inhibitors
• History of gastric bypass
• Evidence of slowed gastric or intestinal motility

Participants have been consented for data sharing. Only anonymised data would be shared.